Safety and Pharmacokinetics of AT1001 (Migalastat HCl) in Healthy Subjects and Subjects With Impaired Renal Function
An Open-Label Study to Determine the Safety and Pharmacokinetics of AT1001 in Subjects With Impaired Renal Function and Healthy Subjects With Normal Renal Function (AT1001-015)
調査の概要
詳細な説明
This will be an open-label, non-randomized, multiple-center, sequential group, safety, tolerability, and PK study of a single dose of AT1001 (migalastat HCl, GR181413A) administered orally as a 150 mg dose in fasted healthy control male and female subjects with normal renal function compared to mild, moderate, and severe renally-impaired subjects (classified by level of creatinine clearance [CLcr] as determined by the Cockcroft-Gault formula).
Screening will occur from Day -28 to Day -2. Subjects will check-in to the clinic on Day -1 and receive a single oral dose of 150 mg AT1001 on Day 1. Subjects will be discharged from the clinic on Day 2 (if stable as determined by the Investigator) and return for daily visits on Day 3 through Day 6 for a safety assessment and PK sampling. Subjects will undergo a follow-up visit on Day 7 (+1) and an end of study visit on Day 10 (+1).
研究の種類
入学 (実際)
段階
- フェーズ 1
連絡先と場所
研究場所
-
-
California
-
Costa Mesa、California、アメリカ、92626
- GSK Investigational Site
-
-
Florida
-
Miami、Florida、アメリカ、33169
- GSK Investigational Site
-
Miami、Florida、アメリカ、33014
- GSK Investigational Site
-
Orlando、Florida、アメリカ、32809
- GSK Investigational Site
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria All subjects
- males or females aged 18 to 70 years inclusive (subjects with normal renal function, mild or moderate renal impairment), and 18 to 75 years inclusive (subjects with severe renal impairment)
- body mass index 18.0 to 40.0 kilogram (kg)/square meter (m^2) inclusive
- females who are non-pregnant, non-lactating, or postmenopausal for >=1 year, surgically sterile for >= 90 days, or agree to use approved methods of contraception
- males will be sterile or use approved methods of contraception
- understands and signs informed consent form Healthy subjects with normal renal function
- negative test for selected drugs of abuse (excludes alcohol) at Screening and Check-in
- good health with no clinically significant medical history, physical examination, vital signs, or 12-lead ECG
- clinical laboratory tests within the reference range or not clinically significant
- normal renal function (estimated CLcr >90 mL/min) at Screening Subjects with mild, moderate or severe renal impairment
- negative test for selected drugs of abuse (excludes alcohol) at Screening and Check-in or verification of a prescription for a positive test
- renal impairment (estimated CLcr <90 mL/min)
- evidence of stable renal impairment defined as two separate estimated CLcr values within 25%
- clinical laboratory results consistent with their renal condition or of no clinical significance for the study
- abnormal laboratory values must not be clinically significant. Anemia secondary to renal disease is acceptable if hemoglobin is ≥9 g/dL and no clinically significant symptoms. Liver enzymes and bilirubin must be below twice the upper normal level
- subjects with renal impairment must have stable underlying medical conditions < 90 days before study start
- stable medication regimen(s) (no new drug(s) or changed dosage(s) <30 days before study drug)
- in good general health, allowing for concurrent illnesses associated with chronic kidney disease
Exclusion Criteria:
All subjects:
- history of hypersensitivity or allergies to any drug, unless approved by the Investigator and reviewed by Sponsor/Medical Monitor
- participation in a study with receipt of an investigational drug < 5 half-lives or 30 days (whichever is longer) before Check-in
- use of alcohol, grapefruit, or caffeine-containing foods or beverages < 72 hours before Check-in, unless approved by the Investigator and reviewed by the Sponsor/Medical Monitor
- poor peripheral venous access
- whole blood donation < 56 days before dosing or plasma donation < 14 days before dosing
- receipt of blood products < 2 months before Check-in
- history or presence of any clinically significant abnormal ECG
- history of alcoholism or drug addiction < 1 year before Check-in
- positive test for HIV antibody, HBsAg or anti-HCV
- pregnant or breastfeeding
Healthy subjects with normal renal function:
- use of any tobacco- or nicotine-containing products < 6 months before Check-in
- clinically significant (history of or active) cardiac, hepatic, pulmonary, endocrine, neurological, infectious, gastrointestinal, hematologic, oncologic, or psychiatric disease putting the subject at increased risk or could interfere with study objectives
- screening laboratory values outside normal range and deemed clinically significant by the Investigator
- use of a prescription drug < 14 days of dosing or a non-prescription drug < 7 days before dosing or need of concomitant medication during the study
Subjects with mild, moderate, or severe renal impairment:
- unstable disease (concurrent medical conditions that have changed significantly < 90 days)
- changes in concomitant prescription medications < 30 days before dosing or expected changes during study
- use of new non-prescription medication < 30 days before dosing
- renal transplant
- acute or chronic non-renal condition limiting the subject's ability to complete and/or participate in the study
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:処理
- 割り当て:なし
- 介入モデル:単一グループの割り当て
- マスキング:なし(オープンラベル)
武器と介入
参加者グループ / アーム |
介入・治療 |
---|---|
実験的:AT1001 150 mg
Each subject will receive a single oral dose of AT1001 150 mg administered orally with 240 mL room temperature water after at least a 4-hour fast
|
AT1001 150mg is available as a capsule
他の名前:
|
この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Number of subjects with adverse events to assess safety and tolerability
時間枠:Day 1 to Day 10 (+1)
|
Adverse events will be evaluated from Day 1 to the end of study (Day 10 +1).
|
Day 1 to Day 10 (+1)
|
Clinical laboratory test values to assess safety and tolerability
時間枠:Day -28 to Day 10 (+1)
|
Clinical laboratory evaluations (hematology, clinical chemistry, urinalysis, Hepatitis A and HIV screen) will be evaluated from screening to the end of the study.
|
Day -28 to Day 10 (+1)
|
Vital signs to assess safety and tolerability
時間枠:Day -28 to Day 10 (+1)
|
Vital signs (oral temperature, respiratory rate, and seated blood pressure) will be performed from screening to the end of the study.
|
Day -28 to Day 10 (+1)
|
Physician examination to assess safety and tolerability
時間枠:Day -28 to Day 10 (+1)
|
Physical examination (general appearance, skin, thorax/lungs, cardiovascular and abdomen) will be performed from screening to the end of the study.
|
Day -28 to Day 10 (+1)
|
Measure of ECG to assess safety and tolerability
時間枠:Day -28 to Day 10 (+1)
|
Electrocardiogram (ECG) measures the electrical activity of the heart and the hearts' rhythm.
All subjects will undergo ECG testing.
|
Day -28 to Day 10 (+1)
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
---|---|---|
Maximum observed concentration (Cmax) of AT1001
時間枠:Day 1 to Day 6
|
Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and the resultant maximum plasma concentration (Cmax) will be measured in subjects with impaired renal function and normal renal function.
|
Day 1 to Day 6
|
Time to achieve maximum concentration (Tmax) of AT1001
時間枠:Day 1 to Day 6
|
Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and time to maximum concentration (tmax) will be measured in subjects with impaired renal function and normal renal function.
|
Day 1 to Day 6
|
Apparent terminal elimination half life (t1/2 ) of AT1001
時間枠:Day 1 to Day 6
|
Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and and apparent terminal elimination half-life (t1/2) will be measured in subjects with impaired renal function and normal renal function.
|
Day 1 to Day 6
|
Area under the concentration-time curve from time zero to the last measurable concentration (AUC 0-t ) of AT1001
時間枠:Day 1 to Day 6
|
Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and AUC 0-t will be measured in subjects with impaired renal function and normal renal function
|
Day 1 to Day 6
|
Area under the concentration-time curve extrapolated to infinity (AUC 0-inf) of AT1001
時間枠:Day 1 to Day 6
|
Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and AUC 0-inf will be measured in subjects with impaired renal function and normal renal function
|
Day 1 to Day 6
|
Apparent terminal elimination rate constant for AT1001
時間枠:Day 1 to Day 6
|
Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and the apparent terminal elimination rate constant will be measured in subjects with impaired renal function and normal renal function
|
Day 1 to Day 6
|
Oral clearance of AT1001
時間枠:Day 1 to Day 6
|
Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and the oral clearance will be measured in subjects with impaired renal function and normal renal function
|
Day 1 to Day 6
|
Oral volume of distribution of AT1001
時間枠:Day 1 to Day 6
|
Blood samples will be collected at predose, and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 15, 24, 48, 72, 96, and 120 hours post-dose and the oral volume of distribution will be measured in subjects with impaired renal function and normal renal function
|
Day 1 to Day 6
|
協力者と研究者
スポンサー
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 116431
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
ファブリー病の臨床試験
-
Adelphi Values LLCBlueprint Medicines Corporation完了肥満細胞性白血病 (MCL) | 攻撃的な全身性肥満細胞症 (ASM) | SM w Assoc Clonal Hema Non-mast Cell Lineage Disease (SM-AHNMD) | くすぶり全身性肥満細胞症 (SSM) | 無痛性全身性肥満細胞症 (ISM) ISM サブグループが完全に募集されましたアメリカ
AT1001 150 mgの臨床試験
-
Fondazione Oncotechまだ募集していません
-
H. Lee Moffitt Cancer Center and Research InstituteGenentech, Inc.募集
-
Instituto Nacional de Cancerologia de Mexico募集
-
Merck Sharp & Dohme LLC完了ヒト免疫不全ウイルス-1 (HIV-1)
-
Hoffmann-La RochePfizer完了中等度から重度の潰瘍性大腸炎アメリカ, オーストラリア, タイ, ポーランド, ロシア連邦, 日本, コロンビア, スペイン, 七面鳥, ルーマニア, インド, スロバキア, フランス, ハンガリー, 南アフリカ, ベルギー, ブルガリア, ドイツ, イタリア, メキシコ, セルビア, ウクライナ, イギリス
-
Reata, a wholly owned subsidiary of BiogenAbbVie; Friedreich's Ataxia Research Alliance積極的、募集していない